We shall explore the hypothesis that inhibitory processes within the cochlear nucleus modify the functional response of the brain to ongoing acoustic stimuli. Our approach is to determine the structural and neurochemical bases for the effects of local circuits on information processing in the cochlear nucleus and to link these findings to the physiological observations made on the same circuits in a companion project. The reciprocal, and possibly inhibitory, connections between specific types of neurons in the ventral and dorsal cochlear nucleus will be defined and their putative neurotransmitters localized. The plan is to identify the neuronal types involved in reciprocal connections between these nuclei by combining anterograde and retrograde tracing methods with the locations of the labeled neurons. The distribution of the synaptic endings on the labeled neurons will be mapped in their respective target areas in order to estimate their potential spheres of influence, to see if there is a discrete mapping of interconnections between neurons or if they project more diffusely to larger domains, corresponding to frequency bands of certain dimensions. Light and electron microscopic immunocytochemistry will be used in combination with anterograde and retrograde tracers to determine which of these projections supplies endings containing the inhibitory transmitters, glycine or GABA, to their target cells. The anatomical findings will be related to the physiological data by combining microscopic labeling of the reciprocal connections and physiological recording of the alterations in acoustical response properties induced by stimulating or inhibiting these connections. In the long term these studies will extend to other nuclei of the brain stem and their interconnections with the cochlear nucleus. This research will elucidate the roles of local circuits and inhibitory interneurons in monaural and binaural hearing. Ultimately they should provide insight into the neurobiology of perceptual phenomena, such as monaural echo suppression, binaural interactions, such as the precedence effect, and sensory control mechanisms in general.